A blueprint for broadly effective bacteriophage-antibiotic cocktails against bacterial infections
Year: 2024
Type: article
Abstract: Bacteriophage (phage) therapy is a promising therapeutic modality for multidrug-resistant bacterial infections, but its application is mainly limited to personalized therapy due to the narrow host range of individual phages. While phage cocktails targeting all possible bacterial receptors could theoretically confer broad coverage, the extensive diversity of bacteria and the complexity of phage-phage interactions render this approach challenging. Here, using screening protocols for identifying “complementarity groups” of phages using non-redundant receptors, we generate effective, broad-range phage cocktails that prevent the emergence of bacterial resistance. We also discover characteristic interactions between phage complementarity groups and particular antibiotic classes, facilitating the prediction of phage-antibiotic as well as phage-phage interactions. Using this strategy, we create three phage-antibiotic cocktails, each demonstrating efficacy against ≥96% of 153 Pseudomonas aeruginosa clinical isolates, including biofilm cultures, and demonstrate comparable efficacy in an in vivo wound infection model. We similarly develop effective Staphylococcus aureus phage-antibiotic cocktails and demonstrate their utility of combined cocktails against polymicrobial (mixed P. aeruginosa/S. aureus) cultures, highlighting the broad applicability of this approach. These studies establish a blueprint for the development of effective, broad-spectrum phage-antibiotic cocktails, paving the way for off-the-shelf phage-based therapeutics to combat multidrug-resistant bacterial infections. The application of phage therapy for multidrug-resistant infections is mainly limited to personalized therapy due to the narrow host range of individual phages. Here, Kim et al. identify groups of phages that use non-redundant receptors, and present a blueprint for the development of effective, broad-spectrum phage-antibiotic combinations.
Source: Nature Communications
Institutions: Stanford Medicine, Stanford University
Language: English
Subfield: Ecology
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: U.S. Department of Health and Human Services, Cystic Fibrosis Foundation, Princeton University, Dartmouth College, University of Montana, Emerson Collective, KU Leuven, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute on Deafness and Other Communication Disorders, National Institute of Allergy and Infectious Diseases
Awards: G110980855, G1255689919, G1753091154, G2867469396, G3088175636, G3659496387, G5245903814, G5935607831, Pathogenesis of Pf Bacteriophages in Pseudomonas Cystic Fibrosis lung Infections, G6601193818, G9000058655, G9000168049, Bacteriophage as a predictive biomarker in chronic Pseudomonas airway disease
OpenAlex ID: W4404825033